Cleft lip and/or palate (CL/P) is a congenital anomaly that is characterized by improper fusion of the upper lip and/or palate. Individuals with CL/P may also suffer from mild cognitive deficits and reading disabilities that are similar to developmental dyslexia. Recent neuroanatomical studies in individuals with CL/P indicate that these cognitive deficits may be associated with abnormal brain structure and development. In alignment with the NIDCR's mission to (1) understand the biological basis of craniofacial disease, (2) to mitigate the effects of craniofacial disease on public health through basic science, behavioral, and clinical research, and (3) to mentor individuals from areas traditionally considered outside of oral and dental health, the proposed training project will characterize the brain morphology of children with CL/P and assess its relationship to known language deficits. The first part of the project is an intra- and inter-observer landmark validation study. Once reliable landmarks are established, magnetic resonance scans of the brains of children with CL/P and matched controls will be landmarked and gross brain shape will be compared between the two groups using statistical shape analysis. Landmark-based shape analysis and volumetrics will also be used to test for structural differences in the inferior frontal gyrus, the superior temporal gyrus, and corpus callosum. Identified structural changes will be regressed against cognitive data (e.g., IQ, verbal fluency, rapid verbal labeling) to determine whether this dysmorphology is associated with poorer performance on intelligence, language, and memory tests and an increased risk for reading disabilities. The proposed project will be the first to test for abnormalities in gross brain shape and in the structure of major language areas in children with CL/P and to determine whether identified changes in brain structure are correlated with known language deficits. By identifying specific areas of the brain that develop abnormally, the possible genetic underpinnings of CL/P can be limited to factors that can directly or indirectly affect both facial structure and regional brain development. Similarly, links between CL/P and developmental dyslexia would provide additional evidence for aberrant neural crest cell migration in this population and would stress the importance of informing parents that their child with CL/P is at an increased risk for reading disabilities. PUBLIC HEALTH RELEVANCE: As one of the most common birth defects in the world, cleft lip and/or palate (CL/P) is of great concern to public health. The proposed project will help to elucidate the basis for the cognitive deficits exhibited by many individuals with CL/P and will provide insight into the etiology of this congenital anomaly by determining whether children with CL/P exhibit structural brain abnormalities associated with language and memory deficits. The proposed project may also identify neuroanatomical abnormalities linked to an increased risk for reading disabilities in this population that may eventually be able to be used for early detection of reading disabilities and thus earlier treatment.